Plastic-Reconstructive Treatment Algorithm for Dead Space Management Following Septic Total Hip Arthroplasty Removal: AV Loop and Two-Stage Free Myocutaneous Latissimus Dorsi Flap.
A 61-year-old patient presented with a right Girdlestone hip and wound dehiscence due to extensive dead space after radical debridement and septic arthroplasty removal. A two-stage reconstruction with the application of a subcutaneous autologous arterio-venous (AV) loop using an autologous vena saphena magna (VSM) interposition graft followed by a free latissimus dorsi flap was performed. We decided to perform a two-stage procedure with AV loop creation in the first step and free flap transplantation seven days after it. In the first step, an AV vascular loop was prepared by transplanting the contralateral VSM interposition graft to the inguinal femoral vessels with subcutaneous passage of the venous loop. In the second step after 7 days, the wound was closed by a two-team approach. One surgical team completed the wound debridement, while the other team harvested the flap by microsurgical preparation of the thoracodorsal pedicle in the right axilla. Upon completed harvest, the flap was placed into the wound to fill the periosseous dead space, and the anastomosis was performed in an end-to-end fashion. The patient remained free of infection with a well-healed flap. He was mobilized on crutches with partial weight bearing on the operated leg. A lower extremity prosthesis with pelvic support was customized.


Type, intensity and duration of daily physical activities performed by adults with spinal cord injury.
Secondary analysis of cross-sectional data. To describe and compare (1) self-reported intensities and durations of specific types of daily physical activities and (2) minutes per day spent on daily physical activities across key demographic groups. Community (Ontario, Canada). Participants were 695 adults with spinal cord injury (SCI; 76% male, Mage=46.81±13.41 years, Myears post injury=15.19±11.10 years). Daily activities were assessed over the telephone using the Physical Activity Recall Assessment for People with SCI. Multivariate analyses of variance (MANOVA) were computed to test for differences in intensities and durations of different daily activities (objective 1) and between-group differences in minutes per day of daily activities (objective 2). Overall, participants reported 127.92±142.79 min per day of daily physical activities with significantly more time spent in mild intensity (78.93±104.62 min per day) than moderate- (40.23±68.71 min per day) or heavy-intensity activities (8.75±24.53 min per day). Four patterns emerged with respect to type, duration and intensity, with some activities being typically performed at lighter or heavier intensities than others. There were significant differences in minutes per day of activity intensity and duration between groups based on education, injury severity and mode of mobility (P<0.05). Given that some groups were more likely to engage in moderate-heavy-intensity activities, and some activities were more likely to be performed at moderate-heavy intensities, interventions that target key groups to increase certain daily activities may be one strategy to enhance overall physical activity participation among people with SCI.


Small Intestinal Angioectasias Are Not Randomly Distributed in the Small Bowel and Most May Be Reached by Push Enteroscopy.
The goal was to describe the location of angioectasias within small bowel on capsule endoscopy and the utility of push enteroscopy versus deep enteroscopy in treatment of overt bleeding from these. Overt bleeding from small bowel angioectasias is a clinical challenge. Thalidomide and octreotide can be difficult to prescribe and may not be effective. Endoscopy remains a mainstay of treatment for overt bleeding from angioectasias but data regarding the long-term efficacy of endoscopic therapy are limited. We sought to define the location of small bowel angioectasias using capsule endoscopy and review our outcomes for push and double-balloon enteroscopy. We retrospectively reviewed all 428 capsule endoscopy studies from the Veterans Administration Hospital in West Haven, CT from 2005 to 2012. Location of angioectasias was evaluated using lead mapping and small bowel transit time. We identified 69 patients with small bowel angioectasia. At least 66.8% of lesions were in duodenum or ligament of Treitz, with 78.3% within the first 25% of small bowel transit. Twenty-four patients underwent endoscopic treatment of overt bleeding from small bowel angioectasias. Thirty-three percent rebled requiring multiple procedures. Eight patients had 10 anterograde double-balloon examinations. Only 2 patients had both cessation of bleeding with double balloon and lesions outside the reach of push enteroscopy. Push enteroscopy for bleeding angioectasias is effective in many patients. Deep enteroscopy may not benefit most patients as most angioectasias are proximal. Patients with deeper lesions tended to have multiple lesions and rebleeding despite deep enteroscopy.


A clinical comparison of 2 electric toothbrush designs.
A single blind 30 day study compared the reduction of plaque and gingivitis for the Hapika Powerbrush to the Interplak ultra 10 tuft. A longitudinal parallel group design was utilized and screening evaluation was performed to determine patient eligibility prior to study enrollment, 66 subjects were entered into the study and assigned to 1 of 2 groups, each using one of the toothbrushes. At baseline, subjects received an oral soft tissue exam, a dental hard tissue exam, and were scored by the Lobene modification of the Löe and Silness gingival index (GI). Plaque was then disclosed and scored both pre and post brushing using the modified Turesky plaque/debris examination and an interproximal bleeding examination was performed post-brushing. On days 15 and 30, after an oral soft tissue and GI examination, plaque was graded by the Modified Turesky plaque/debris exam. Subjects then brushed and were graded by the Modified Turesky plaque/debris examination and an interproximal bleeding index examination. The results showed that both brushes provided a similar change in clinical indices. All produced a statistically significant reduction from baseline to day 30 for the gingival index (26.5-29.1%), the bleeding index (13.8-24.1%), and the plaque index (16.9-19.4%). A comparison of pre and post brushing scores for the plaque index at 30 showed that both brushes reduced plaque similarly with a statistically significant reduction (P < 0.05) from their pre-brushing plaque index scores at all time periods.


Common enterobacterial antigen in Yersinia enterocolitica.
Production of the common enterobacterial antigen (CA) by strains of Yersinia enterocolitica (Y.e.) serotypes 3 and 9 (Winblad), by strains of 5 different Y.e. serogroups (Wauters) and various other bacteria was examined. Antibody against CA was raised by immunization of rabbits with E. coli O 14. Extract prepared from S. typhimurium was used for the sensitization of sheep erythrocytes with CA. Absorption and haemagglutination inhibition experiments showed that CA could be detected in heat extracts from all Y.e. strains examined, and in that from Yersinia pseudotuberculosis. CA was not detected in extracts from Pasteurella multocida, Francisella tularensis, Brucella abortus, Acinetobacter calcoaceticus or Pseudomonas aeruginosa. Anti-CA antibodies could not be demonstrated in serum from rabbits immunized with Y.e. bacteria, but were demonstrated in serum from rabbits immunized with a CA-containing fraction of the Y.e. extract. The possibility of participation of anti-CA antibody in indirect haemagglutination tests for detection of antibody to Y.e. O antigens is emphasized.


A comparison of the availability of tobramycin for inhalation from vented vs unvented nebulizers.
To compare drug output from a vented nebulizer (Pari LC Jet Plus) with a traditional unvented nebulizer (Hudson 1730 T Up-Draft 11) using aerosolized tobramycin, which is frequently used in the treatment of cystic fibrosis. Six nebulizers of each type were filled with a 4 mL tobramycin (80 mg) solution and were driven by a compressor (Pulmo-Aide). Various inspiratory flows (VI) (0, 5, 10, 15, 20 L/min for the Pari LC Jet Plus and 0, 5, and 10 L/min for the Hudson 1730, all at 40% relative humidity) were directed through each nebulizer. Drug output was measured from changes in weight and concentration (assessed by changes in osmometry) within the nebulizer. Particle size distributions were determined by laser diffraction allowing the calculation of the amount of aerosol output in the respirable range (<5 microm). The nebulizers were first run until end-nebulization to establish total drug output and then for either 4 or 5 min to determine the rate of drug output (mg/min) before intermittent aerosol output. The total drug output without VI for both the unvented and the vented nebulizers was not significantly different, 55 (51, 60) mg for the Hudson 1730 vs 51 (49, 53) mg for the Pari LC Jet Plus (mean [95% confidence limits]). Inspiratory flow had no effect on the unvented Hudson 1730 nebulizer but significantly increased the rate of total drug output and the rate of drug output in the respirable range for the vented Pari LC Jet Plus nebulizer (VI=0, 3.35 [2.84, 3.85] and 1.72 [1.48, 1.96] compared with VI=20, 9.87 [9.03, 10.70] and 6.11 [5.33, 6.88] mg/min). These findings indicate that the increase in the rate of drug output with VI for the vented nebulizer would result in shorter nebulization times and a relative decrease in drug loss during the expiratory phase.


Cytotoxic monotetrahydrofuran acetogenins from Disepalum plagioneurum.
The known plagionicin A (1) and eight new monotetrahydrofuran acetogenins, plagionicins B-D (2-4) and plagioneurins A-E (5-9), were isolated from the leaves of Disepalum plagioneurum by bioassay-guided purification. The structures of the new compounds were elucidated by spectroscopic methods. The new monotetrahydrofuran (mono-THF) acetogenins exhibited significant in vitro cytotoxicity against the KB cancer cell line, with IC(50) values in the nanomolar range.


The Role of Racial and Ethnic Factors in MicroRNA Expression and Risk for Type 2 Diabetes.
Prior studies focused on circulating microRNAs and the risk for complex diseases have shown inconsistent findings. The majority of studies focused on European and East Asian racial or ethnic groups, however, ancestry was not typically reported. We evaluated the risk for type 2 diabetes as an exemplar to show that race and ethnic group may contribute to inconsistent validation of previous findings of associations with microRNAs.


Can We Arrest the Evolution of Antibiotic Resistance? The Differences between the Effects of Silver Nanoparticles and Silver Ions.
Silver nanoparticles (AgNPs) are effective antimicrobial substances that show promise in combatting multidrug resistance. The potential application and release of AgNPs into the environment may neutralize the selective advantage of antibiotic resistance. Systemic knowledge regarding the effect of NPs on the evolution of antibiotic resistance is lacking. Our results showed that bacteria slowly developed adaptive tolerance to ciprofloxacin (CIP) under cyclic CIP and silver ion (Ag+) cotreatment, and no resistance/tolerance was discernible when CIP and AgNP exposure was alternated. In contrast, rapid CIP resistance was induced under continuous selection by treatment with only CIP. To combat the effects of CIP and Ag+, bacteria developed convergent evolutionary strategies with similar adaptive mechanisms, including anaerobic respiration transitioning (to reduce oxidative stress) and stringent response (to survive harsh environments). Alternating AgNP exposure impeded evolutionary resistance by accelerating B12-dependent folate and methionine cycles, which reestablished DNA synthesis and partially offset high oxidative stress levels, in contrast with the effect of CIP-directed evolutionary pressure. Nevertheless, CIP/AgNP treatment was ineffective in attenuating virulence, and CIP/Ag+ exposure even induced the virulence-critical type III secretion system. Our results increase the basic understanding of the impacts of NPs on evolutionary biology and suggest prospective nanotechnology applications for arresting evolutionary antibiotic resistance.


[Lowered osmotic resistance of mouse LS fibroblasts grown in the presence of various types of dextran].
Mouse fibroblasts grown in the presence of dextrans of various molecular weight at various concentrations, show a small but significant decrease of the osmotic resistance (Tab. 1,2,3; ANOVA: source of variation A and C); this decrease is related to the length of time the cells stay in the dextran containing medium (Tab. 2,3; ANOVA: source of variation B). The presence of dextran in the culture medium has no effect on the cell growth (Tab. 4).


Aggressive sebaceous carcinoma of the eyelid: an elusive diagnosis.
Sebaceous carcinoma of the eyelid, an extremely rare neoplasm, can resemble blepharitis, conjunctivitis, or chalazion, as in the case presented here. A biopsy specimen should be examined if these conditions fail to respond to therapy, especially if the lesion is unilateral. The tumor can be multifocal, and pagetoid proliferation is common. Therefore, recurrences are common after conservative surgery, even if frozen sections are obtained from the margins. Orbital exenteration may be necessary to prevent metastasis.


Applications of dendrimers for brain delivery and cancer therapy.
Dendrimers are emerging as potential nonviral vectors for the efficient delivery of drugs and nucleic acids to the brain and cancer cells. These polymers are highly branched, 3D macromolecules with modifiable surface functionalities and available internal cavities that make them attractive as delivery systems for drug and gene delivery applications. This article highlights the recent therapeutic advances resulting from the use of dendrimers for brain targeting and cancer treatment.


[An epidemiologic survey of the prevalence of dental caries in 6-15-year-old children in Champagne-Ardennes].
An epidemiological survey of dental caries in Champagne-Ardennes was conducted on a representative sample of 507 schoolchildren aged 6 to 15 years. The dft, DMFT and DMFS indices were analyzed in urban and rural zones. Although slightly lower, they were quite similar to the indices obtained at the national level. The DMFT and DMFS comparison between girls and boys showed the existence of various critical periods where a sudden and important increase in carious lesions was observed. The analysis of the indices assessing the periodontal conditions underlined the necessity of improving the oral education and hygiene.


[An unusual case of pulmonary infiltrates with hepatic involvement in a woman with eosinophilia].
The literature reports many cases of eosinophilic pulmonary infiltrations, with different etiology. In our case clinical pictures were not very clear and specific at first and the clinical course was altered by an ex adjuvantibus steroid treatment before admission to hospital. It was new and unusual because it presented some characteristics of chronic eosinophilic pneumonia and idiopathic hypereosinophilic syndrome, with hepatic involvement as in the former, but without serious heart disease as in the latter. This confirms the difficulties in making a classification of the different clinical pictures because of their indistinct margins, which might appear as different forms of a single disease. In our case the patient refused transbronchial lung biopsy which is commonly considered a minimum diagnostic requirement. Some authors are not in agreement and think it is sufficient to find eosinophils in BAL to start steroid treatment, avoiding biopsy risks. Another interesting finding is the need for a long-term low-dose steroid treatment, to avoid relapses.


Stochastic Resonance Training Improves Balance and Musculoskeletal Well-Being in Office Workers: A Controlled Preventive Intervention Study.
Sixty-two office workers in a Swiss federal department were randomly assigned to a training and a control group. While the training group was instructed to complete 3 stochastic resonance whole-body vibration (SR-WBV) exercises every week for 4 weeks, the control group received no treatment. During this time all participants answered a daily questionnaire concerning their surefootedness, sense of balance, musculoskeletal well-being, and muscle relaxation. Before and after the 4-week SR-WBV intervention, balance was tested with a single-leg stance on a foam mat of the Balance Error Scoring System (BESS) using a SwayStar™-System measuring Total Angle Area (TotAngArea) and Total Velocity Area (TotVelArea). Multilevel results highlighted a significant increase over time for surefootedness and sense of balance (t = 2.491, p = .016), as well as for musculoskeletal well-being and muscle relaxation (t = 2.538, p = .014) in the training group but not in the control group. Balance tests showed improvement of balance in the training group (TotAngArea: Z = 2.550, p = .011; TotVelArea: Z = 3.334, p = .001) but not in the control group. SR-WBV exercise indicated a high compliance during this study (3.87±0.45 trainings per week) underlining its benefits for the working context. Especially office workers who spend most of their time in sitting position could profit from SR-WBV exercise to improve balance and reduce the risk of falls.


Trichomonas vaginalis infection in Nigerian pregnant women and risk factors associated with sexually transmitted infections.
Trichomoniasis poses a public health threat to pregnant women and neonatal health. This study evaluated Trichomonas vaginalis and other common sexually transmitted infections (STIs) status in pregnant women, and risk factors associated with them. The study was cross-sectional and descriptive and a total of 198 pregnant women were recruited for T. vaginalis screening by microscopic examination. Questionnaires were also administered to 108 pregnant women to access information related to socio-demography and other factors associated with STI transmission. The overall prevalence of T. vaginalis was 18.7%. While prevalence of T. vaginalis was neither age nor parity dependent (p > 0.05), women in their first trimester showed significantly higher prevalence of trichomoniasis compared to women in their second and third trimesters (p < 0.05). The frequency of STIs was lowest (18.2%) and highest (71.4%) in age groups ≥ 39 and 15-20 years, respectively. Low levels of education, multiple sexual partners, lack of knowledge on partners' STI history, and having sex under the influence of alcohol or drugs were risk factors of for STIs (p < 0.05). We found a high prevalence of T. vaginalis in pregnant women, with those at an early gestational age at greater risk. The improved education of women on safe sex and the need to know partners' STI status are advocated.


Carbohydrate analysis by desorption electrospray ionization fourier transform ion cyclotron resonance mass spectrometry.
We report the use of desorption electrospray ionization hybrid Fourier transform ion cyclotron resonance mass spectrometry (DESI-FT-ICR-MS) for the analysis of carbohydrates. Spectra of neat carbohydrates are presented along with their mass measurement accuracies and limits of detection. Furthermore, a comparison is made between the analyses of O-linked glycans from mucin by DESI-FT-ICR-MS and matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry. Finally, glycans from mucin are identified by using the high mass measurement accuracy and tandem MS capabilities afforded by the hybrid FT-ICR-MS platform.


[Lactation and sensitivity to corticotropicaxis to stress].
1. The plasma corticosterone levels were measured in nursing female rats which had been removed from their pups for 12 hrs, at 9 a. m. every day till weaning (day 22). The mean value found in this condition (14.6 +/- 2.7 mug/100 ml) does not differ significantly from that found for the cyclic female (13.7 +/- 4.2 mug/100 ml). 2. Suckling for a period of either 3 or 30 min increases the content of plasma corticosterone to the same value ; this value is maximal (+ 22.8 mug/100 ml) 30 min after suckling has started. 3. When mothers have been anaesthetized by a pentobarbital injection 40 min before suckling, plasma corticosterone increase, measured in the same conditions, is lower (+ 12.3 mug/100 ml). 4. The response to psychic (+ 25.5 mug/100 ml) or systemic (+ 46.6 mug/100 ml) stresses in mothers which have been removed from pups for 12 hr is impaired with respect to cyclic females (+ 62.7 mug/100 ml and + 83.8 mug/100 ml respectively). 5. Psychic stress applied immediately after suckling does not increase the plasma corticosterone level ; systemic stress does so slightly (+ 25 mug/100 ml). 6. In lactating rats the response to stress of the hypothalamo-pituitary-adrenal axis seems to be the same as that of intact or castrated males or ovariectomized females ; but differs from the response of cyclic females or of pregnant females when their basal corticosterone level is low.


The Relationship Between Housing Types and Metabolic and Weight Phenotypes: A Nationwide Survey.
Compared to studies evaluating the effect of environmental factors on weight and health, relationships between housing types and health conditions are understudied. This study aimed to assess the relationship between housing types and metabolic and weight phenotypes using data from the 2014 to 2015 Korea National Health and Nutrition Examination Survey. A total of 9586 Korean adults (4128 men and 5458 women; mean age, 50.7 ± 16.5 years) were considered for this study. Four metabolic and weight phenotypes were created using presence/absence of metabolic syndrome and body mass index (<25 kg/m2 for normal weight vs. ≥25 kg/m2 for overweight). Nonapartment residents were 1.23-fold (95% confidence interval: 1.07-1.42) more likely to have metabolically unhealthy and overweight phenotype compared to apartment residents, after adjusting for sociodemographic characteristics, residence area, health behaviors, and nutritional information awareness. In a subgroup analysis, nonapartment living was associated with higher odds for the metabolically unhealthy and overweight phenotype than living in an apartment in individuals with the following characteristics: age <60 years, education ≥ college, second-third quartile income level, married, living in urban area, alcohol <16 drinks/week, noncurrent smokers, and aware of nutritional information. Housing types may be an indicator for increased risk of metabolic and weight phenotypes in Korean adults and used to select high risk individuals. Uncontrolled confounding factors related to housing types, including property assets and environmental attributes, may contribute to the findings.


Hydatid cyst of the neck mimicking a branchial cleft cyst.
Here we report a rare case of primary hydatid cyst with involvement of soft tissue of the neck in a child. A 4-year-old girl presented with gradual swelling of the right side of her neck over a period of several months. The lump was fairly soft and painless with no significant inflammation. There was no other abnormal finding in the physical examination. Imaging was performed by ultrasonography followed by neck CT scan which demonstrated a simple cyst as the cause for the neck bulging. With the presumed diagnosis of a branchial cleft cyst, surgical resection was performed. Hydatid cyst was confirmed in pathology. Isolated soft-tissue hydatid cyst is an uncommon finding which should be considered in the differential diagnosis of soft-tissue cystic lesions especially in endemic regions. This is of more significance in children in whom congenital cysts of head and neck are more common.


Reconstructed human epidermis-based testing strategy of skin sensitization potential and potency classification using epidermal sensitization assay and in silico data.
The hazards and potency of skin sensitizers are traditionally determined using animal tests such as the local lymph node assay (LLNA); however, significant progress has been made in the development of non-animal test methods addressing the first three mechanistic key events of adverse outcome pathway in skin sensitization. We developed the epidermal sensitization assay (EpiSensA), which is a reconstructed human epidermis-based assay, by measuring four genes related to critical keratinocyte responses during skin sensitization. Four in vitro skin sensitization test methods (EpiSensA, direct peptide reactivity assay [DPRA], KeratinoSens™, and human cell line activation test [h-CLAT]) were systematically evaluated using 136 chemicals including lipophilic chemicals and pre/pro-haptens, which may be related to assay-specific limitations. The constructed database included existing and newly generated data. The EpiSensA showed a broader applicability domain and predicted the hazards with 82.4% and 78.8% accuracy than LLNA and human data. The EpiSensA could detect 76 out of 88 sensitizers at lower concentrations than the LLNA, indicating that the EpiSensA has higher sensitivity for the detection of minor sensitizing constituents. These results confirmed the potential use of the EpiSensA in evaluating a mixture of unknown compositions that can be evaluated by animal tests. To combine different information sources, the reconstructed human epidermis-based testing strategy (RTS) was developed based on weighted multiple information from the EpiSensA and TImes MEtabolism Simulator platform for predicting Skin Sensitization (TIMES-SS; RTSv1) or Organization for Economic Cooperation and Development (OECD) QSAR Toolbox automated workflow (RTSv2). The predictivities of the hazards and Globally Harmonized System (GHS) subcategories were equal to or better than the defined approaches (2 out of 3, integrated testing strategy [ITS]v1, and ITSv2) adopted as OECD Guideline 497.


Gene expression profile predicts patient survival of gastric cancer after surgical resection.
This study was conducted to characterize gene expression profile of survival in patients with surgically curable gastric cancer by using an in-house membrane microarray and developing a survival prediction model. Data of cDNA microarrays were obtained from 18 pairs of cancerous and noncancerous gastric tissues. Nine patients who survived > 30 months were identified as good survival, and the other nine, who survived < 12 months, were identified as poor survival. Supervised analysis was performed to identify a gene expression profile by good and poor survival. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the microarray data in 10 patients with sufficient RNA. Using these 10 patients and another 10 patients selected randomly from 40 newly enrolled patients as the training group, the RT-PCR status of the confirmed genes was used for predicting good versus poor survival. Finally, the prediction model was tested in the remaining 30 newly enrolled gastric cancer patients. A survival prediction model consisting of three genes (CD36, SLAM, PIM-1) was developed. This model could correctly predict poor or good survival in 23 (76.7%) of 30 newly enrolled patients, and yielded a specificity of 80% and a sensitivity of 73.3%. The survival rate of the patients predicted to have good survival was significantly higher than that of those predicted to have poor survival in the test group as a whole (N = 30; P = .00531) and in stage III patients (n = 16; P = .04467). The semiquantitative RT-PCR gene expression profiling of three genes extracted from microarray study can accurately predict surgery-related outcome in gastric cancer patients.


Does CyberKnife improve dose distribution versus IMRT and VMAT on a linear accelerator in low-risk prostate cancer?
Hypofractionated stereotactic body radiation therapy (SBRT) for prostate cancer (PCa) can be delivered with the robot-assisted CyberKnife (CK) system or on a linear accelerator using dynamic intensity-modulated radiotherapy (IMRT) or volumetric arc radiotherapy (VMAT). This retrospective study was performed to determine whether CK offers better dose distribution than IMRT and/or VMAT. Treatment plans for three techniques were prepared using the same treatment parameters (36.35 Gy, 7.25 Gy/fr). We evaluated target coverage, conformity index (CI), homogeneity index (HI), gamma index (GI), and organs at risk (OAR) constraints. The mean planning target volume (PTV) dose for CK (39.58 Gy) was significantly greater than VMAT or IMRT (both 36.25 Gy). However, CK resulted in a wider dose range (31.48 to 45.89 Gy) vs. VMAT and IMRT (34.6-38.76 Gy). The mean dose to the rectum (V36Gy, mm3) was significantly lower (p < 0.001) in the CK plans (219.78 vs. 519.59 and 422.62, respectively). The mean bladder dose (V37Gy, mm3) was significantly greater for CK (3256 vs. 1090.75 for VMAT and 4.5 for IMRT (p < 0.001). CK yielded significantly better CI (1.07 vs. 1.17 and 1.25 for VMAT and IMRT, respectively; p < 0.01) and HI values (1.27 vs. 1.07 and 1.04; p < 0.01). GI values for the δd = 3mm, δ% = 3% criteria were 99.86 (VMAT), 99.07 (IMRT) and 99.99 (CK). For δd = 2mm, δ% = 2%, the corresponding values were 98.3, 93.35, and 97.12, respectively. For most variables, CK was superior to both VMAT and IMRT. However, dynamic IMRT techniques, especially VMAT, do not differ significantly from CK plans and are therefore acceptable alternatives to CyberKnife.


[The new frontier of distance learning: the climate of the virtual lecture hall].
The recent ECM standards outline new dilemmas not only under an economic and/or management point of view, but even under a teaching and procedural aspect. FAD seems to solve problems, allowing us to arrange courses according to our demand, but it still doesn't solve all the issues, for example, the teaching-learning model. The article starts analysing formative procedures to reflect in an interactive logic about object and subject in FAD, to set a dynamic learning process in a knowledge management viewpoint, where the user is fully aware that he/she will be divided from his/her tutor and from his/her colleagues in the virtual classroom. The learning environment is a crucial circumstance to assure full functionality of the course and to make the FAD experience a valuable one and repeatable in the future for different courses. FAD is an asynchronous activity and for this it could be moulded according to the single user's requirements. It needs a relational dimension to facilitate the learning process through the strategy sharing of problem solving.


[Experimental study on effect of Suifukang in promoting repairing and regeneration of nerve fibers in spinal cord].
To study the change in expressions of nerve growth related protein (GAP-43) and neurofilament (NF) after experimental injury of spinal cord, and the regulatory effect of Chinese medicine Suifukang (SFK) on them. Forty-eight from the 54 selected adult SD rats were established into spinal cord injury model by making hemitransection at the T12 level, and randomly divided into two groups, the SFK group feed with SKF contained liquor and the model group feeding with equal volume of saline. The another 6 rats were untreated and taken as the normal group. All rats were sacrificed in batches at different time points of day 3, 7, 15 and 30 after modeling. The spinal cord was obtained for determining the optic density (OD) of positive expression of GAP-43 and NF with immunohistochemical stain by microscopic and semi-quantitative image analysis. (1) OD of NF in the model group was obviously decreased on day 7, showing significant difference to that in the normal group and that in the SFK group (P < 0.05), and it maintained at low level after then, while the OD of NF in the SFK group was obviously higher than that in the model group (P < 0.05), it arrived the peak on day 15 and then dropped near the level in the normal group on day 30; (2) OD and of GAP-43 in the model group obviously decreased on day 3 (P < 0.05), showing significant difference to that in the normal group (P < 0.05), then it returned to approach to the level in the normal group on day 7. It was higher in the SFK group than in the model group on day 3, and maintained the high level to day 7, at that time, it was still higher than that in the model group and also higher than that in the normal group (P < 0.05). SFK can promote the repair and regeneration of injured nerve fibers in spinal cord by up-regulating the expression of GAP-43 and NF.


Prediction of rho-independent Escherichia coli transcription terminators. A statistical analysis of their RNA stem-loop structures.
Escherichia coli rho-independent transcription terminators are characterized by an RNA structure having a G+C-rich stem-loop followed by a series of uridine residues, but they can be only partially predicted by the stability of this structure or by its primary sequence. A large number of such terminators have been identified or proposed in the literature, and we have constituted a list of them (148 found in 1021 x 10(3) base-pairs of E. coli DNA sequences) in order to analyze statistically the corresponding RNA hairpins. We show that the size of the loops presents a narrow distribution, that their sequences are not random, and that most loops are closed by a C.G base-pair. In particular, 55% of the loops are tetranucleotides and the most abundant loop sequences are UUCG and GAAA. These loops are abundant in prokaryotic and eukaryotic RNAs, and are known to enhance the stability of RNA hairpins. We propose that these tetraloops play an important role in the nucleation of the nascent RNA structures, as does also the presence of a C.G base-pair closing a hairpin loop. This analysis allows us to propose a model of formation of an RNA hairpin during the termination process and to construct an algorithm of prediction of the terminators in a given DNA sequence. For the E. coli sequences, it clearly distinguishes inter- from intracistronic terminator-like structures, and selects 141 of the 148 rho-independent terminators given in the literature, with a very low background. It also predicts with reasonable accuracy the in vitro termination efficiency of known rho-independent terminators, as well as predicting the existence of 35 as yet uncharacterized terminators.


Next-generation sequencing detection and characterization of a heterozygous novel splice junction mutation in the 2B domain of KRT1 in a family with diffuse palmoplantar keratoderma.
Diffuse palmoplantar keratoderma (DPPK) is an autosomal-dominant genodermatosis characterized by restricted, uniform hyperkeratosis on the palm and sole epidermis. DPPK is normally associated with dominant-negative mutations in the keratin-encoding gene, KRT1. We report a heterozygous novel point mutation in the exon 6 splice donor site of KRT1 (c.1254G>C) by next-generation sequencing, resulting in the formation of two alternative transcripts, which segregates with DPPK in a four-generation Chinese family. This results in both the complete loss of exon 6 and the simultaneous utilization of a novel in-frame splice site 54 bases downstream of the mutation with the subsequent deletion of 42 amino acids and the insertion of 18 amino acids into the protein's 2B domain. This is the first report of a novel splice donor site mutation with aberrant splicing and the formation of two alternative transcripts causing DPPK. This study also demonstrates the value of next-generation sequencing in the identification of novel disease-causing mutations.


Functional evidence for a pH sensor of erythrocyte K-Cl cotransport through inhibition by internal protons and diethylpyrocarbonate.
The sidedness of proton modulation of K-Cl cotransport (K-Cl COT) was studied in low K sheep red blood cells stripped of cellular Mg, Mgi, at alkaline medium pH, pHo, by the divalent ionophore A23187 and a chelator. This procedure activates K-Cl COT, presumably, by inhibition of MgATP-dependent kinases. Ouabain-resistant K efflux and Rb influx were measured in Cl or NO3 either at variable pHi and fixed pHo, or vice versa, in erythrocytes pH- and volume-clamped with the anion exchange inhibitor 4,4'-diisothiocyanato-2,2'-disulfonic stilbene (DIDS) and sucrose. Between pHi 9 and 6, and at constant pHo 9, K effluxes decreased hyperbolically in Cl and linearly in NO3 whereas Rb influxes fell almost linearly in Cl and asymptotically in NO3. Thus, saturation of outward and inward K-Cl COT, the calculated difference of the fluxes in Cl and NO3, occurred at slightly different pHi values. Hill plots revealed pKa values of 6.5 and 7.0, and Hill coefficients of > 1 for outward and inward K-Cl COT, respectively. Raising pHo from 6 to 9 at fixed pHi slightly increased K and Rb fluxes in both Cl or NO3, but not K-Cl COT. The histidine reagent diethylpyrocarbonate (DEPC) inhibited low Mgi-activated K-Cl COT at approximately 4 mM, an effect partially reversible by subsequent treatment with hydroxylamine. It is concluded that protons inhibit erythrocyte K-Cl COT through internal histidine(s) which may be part of a pH sensor.


Archaeal lipid mucosal vaccine adjuvant and delivery system.
Archaeal polar lipids are being evaluated as adjuvants/vaccine delivery systems for mucosal vaccines that can provide protection against pathogens that enter the human host via the mucosal surfaces. Archaeosomes, liposomes made from polar lipids extracted from Archaea, with encapsulated antigens elicit strong antigen-specific systemic immune responses upon systemic or intranasal immunization, but fail to generate mucosal immune responses. However, intranasal immunization of mice with the archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) system, obtained by the interaction of archaeosomes/antigens with multivalent cations, induces robust, antigen-specific IgA responses in nasal and vaginal mucosa, feces, bile, and serum. In addition, strong antigen-specific systemic antibody (serum IgG, IgG(1) and IgG(2a)) and cell-mediated responses, including CD8(+) cytotoxic T lymphocyte, are generated. The responses are sustained over time and are subject to good memory-boost responses. The AMVAD formulations are stable during storage, have a good safety profile and show protective efficacy in a murine model of infection/challenge.


The vibrational spectrum of NF3 and the manifestation of resonant dipole-dipole interaction in NF3 solutions in liquid argon.
Vibrational spectra of trifluoramine, NF3, dissolved in liquid Ar were studied at 90 K in the concentration range between 2 x 10(-5) and 0.1 mole fraction, using Fourier transform spectroscopy. The concentration dependence of the band shapes in the region of the combination transitions nu1+nu3, nu2+nu3, and 2nu3 involving the strong nu3 mode was studied and the absorption associated with NF3 dimers was isolated. This absorption is compared with spectra of NF3 dimers calculated on the basis of resonant dipole-dipole interaction between two doubly degenerate oscillators. Spectra of pure liquid NF3 were recorded for comparison. Using the nu1+nu3 absorption band of the NF3 dimer the distance R between two NF3 molecules was determined to be R=4.5(1) A in solution in liquid Ar. This distance is compared with the separation between two NF3 molecules in liquid NF3 and with the value calculated from the pair distribution function obtained from Monte Carlo simulations.


[Blood coagulation parameters in patients with lichen planus].
The aim of this study was to evaluate some blood parameters of coagulation process in blood plasma of patients suffering from lichen planus. The study group consisted of 23 patients--14 women and 9 men, aged 33-75 years. Control group contained 30-age matched healthy persons. In blood of plasma the following parameters were determined: activity of antithrombin III (AT III) and concentration of prothrombin fragments 1+2 (F1+2), complexes thrombin-antithrombin III (TAT). In blood plasma of patients with lichen planus the concentration of F1+2 was significantly higher than in healthy persons. Increased concentration of F1+2 indicated intensive thrombinogenesis in vivo in patients with lichen planus.


Ruthenium-Catalyzed Azide-Thioalkyne Cycloadditions in Aqueous Media: A Mild, Orthogonal, and Biocompatible Chemical Ligation.
The development of efficient metal-promoted bioorthogonal ligations remains as a major scientific challenge. Demonstrated herein is that azides undergo efficient and regioselective room-temperature annulations with thioalkynes in aqueous milieu when treated with catalytic amounts of a suitable ruthenium complex. The reaction is compatible with different biomolecules, and can be carried out in complex aqueous mixtures such as phosphate buffered saline, cell lysates, fetal bovine serum, and even living bacteria (E. coli). Importantly, the reaction is mutually compatible with the classical CuAAC.


Educational intervention improves knowledge and adherence to treatment amongst puerperal women with syphilis: randomized clinical trial.
Gestational syphilis requires early detection and proper treatment to prevent negative maternal-fetal outcomes. This study aimed to evaluate the effectiveness of an educational intervention on treatment adherence and knowledge about syphilis in postpartum women with positive Treponema pallidum results. A randomized, parallel, and open clinical trial was conducted with 64 postpartum women who tested positive for T. pallidum, assigned to two groups (1:1 ratio). The Intervention Group (IG) received an educational intervention on syphilis, including an explanatory leaflet and hands-on demonstrations, along with standard guidelines. The Control Group (CG) received standard guidelines alone. Pre-test and post-test assessments were conducted to measure knowledge and treatment adherence. Statistical analyses included descriptive and inferential methods, assessing group homogeneity using the Chi-square or Fishers exact test. The interventions effectiveness was determined using relative risk, and pre- and post-test scores were compared using the independent t test. The post-test revealed improvements in knowledge scores for general knowledge, treatment, and prevention domains (p < .05). The IG demonstrated an increase in post-test knowledge scores (p = .001), with association between post-test scores and treatment adherence (p = .001). The educational intervention on syphilis improved knowledge and treatment adherence in postpartum women with syphilis.


Valacyclovir as Initial Treatment for Acute Retinal Necrosis: A Pharmacokinetic Modeling and Simulation Study.
Acute retinal necrosis (ARN) is a feared complication of infectious retinitis most commonly caused by varicella zoster virus (VZV). We performed a pharmacokinetic modeling and simulation study by integrating the existing understanding of physiology with previously published data to evaluate the vitreal penetration of oral valacyclovir for the treatment of ARN, under various dosing scenarios. We compared different oral valacyclovir dosing regimens with intravenous acyclovir. The vitreous compartment was modeled as a peripheral compartment, and paired serum and vitreal acyclovir concentrations were obtained from previously published data of adult patients with ARN undergoing vitrectomy. The efficacy threshold for vitreal acyclovir concentrations was based on the previously reported IC50 values for VZV. Based on the minimum vitreal acyclovir concentrations (Cmin) relative to the mean IC50 for VZV, valacyclovir 1.5 g every 8 hours performed similarly to intravenous acyclovir 700 mg every 8 hours, with the minimum concentration (Cmin) exceeding the mean IC50 after the second dose. In contrast, the standard dosing regimen for herpes zoster, valacyclovir 1 g every 8 hours, performed inferiorly to the intravenous acyclovir regimen throughout the dosing interval. Modeling and simulation data support oral valacyclovir for the treatment of ARN, although the required dosing exceeds the recommended FDA dose size for herpes zoster.


A 12-connected metal-organic framework constructed from an unprecedented cyclic dodecanuclear copper cluster.
A 12-connected metal-organic framework based on an unprecedented cyclic Cu(12) cluster with a large internal cavity has been prepared, and its cation exchange property was determined.


Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein.
Hepatitis C virus (HCV) is the major cause of non-A non-B hepatitis and a leading cause of liver dysfunction worldwide. While the current therapy for chronic HCV infection is parenteral administration of type 1 interferon (IFN), only a fraction of HCV-infected individuals completely respond to treatment. Previous studies have correlated the IFN sensitivity of strain HCV-1b with mutations within a discrete region of the viral nonstructural 5A protein (NS5A), termed the interferon sensitivity determining region (ISDR), suggesting that NS5A may contribute to the IFN-resistant phenotype of HCV. To determine the importance of HCV NS5A and the NS5A ISDR in mediating HCV IFN resistance, we tested whether the NS5A protein could regulate the IFN-induced protein kinase, PKR, a mediator of IFN-induced antiviral resistance and a target of viral and cellular inhibitors. Using multiple approaches, including biochemical, transfection, and yeast genetics analyses, we can now report that NS5A represses PKR through a direct interaction with the protein kinase catalytic domain and that both PKR repression and interaction requires the ISDR. Thus, inactivation of PKR may be one mechanism by which HCV avoids the antiviral effects of IFN. Finally the inhibition of the PKR protein kinase, by NS5A is the first described function for this HCV protein.


Amniotic Fluid L-Type Fatty Acid-Binding Protein in Predicting Fetal Condition.
Ultrasonography and fetal heart rate monitoring are subjective assessments of fetal condition, which warrants the need for objective markers to predict fetal condition. Urinary L-type fatty acid-binding protein (L-FABP) levels correlate with hypoperfusion. Elevated amniotic fluid L-FABP levels may represent fetal tissue hypoperfusion since the amniotic fluid contains fetal urine. In this study, we aimed to analyze the effectiveness of amniotic fluid L-FABP as a predictor of fetal condition. We classified singleton pregnancies into groups based on fetal growth restriction (FGR) with and without fetal blood flow abnormalities (FGR and healthy-FGR groups, respectively) and the non-FGR group (control group). We collected amniotic fluid at the time of vaginal delivery, cesarean section and amniocentesis, and compared the patient characteristics, clinical outcomes and amniotic fluid levels of L-FABP between the groups. We analyzed 153 singleton pregnancies and 186 amniotic fluid samples (FGR group, 6 (3.9%) pregnancies and 23 (12.4%) samples; healthy-FGR group, 15 (9.8%) pregnancies and 20 (10.7%) samples; control group, 132 (86.3%) pregnancies and 143 (76.9%) samples). The amniotic fluid L-FABP level was significantly higher in the FGR group compared to that in the healthy-FGR and control groups. Multivariate analysis revealed that the amniotic fluid L-FABP level was not affected by fetal body weight. Additionally, the amniotic fluid L-FABP levels increased significantly in cases with fetal blood flow abnormalities or early gestational age. Therefore, amniotic fluid L-FABP level may be an objective and accurate predictive marker of fetal condition.


Mapping the connectivity of serotonin transporter immunoreactive axons to excitatory and inhibitory neurochemical synapses in the mouse limbic brain.
Serotonin neurons arise from the brainstem raphe nuclei and send their projections throughout the brain to release 5-HT which acts as a modulator of several neuronal populations. Previous electron microscopy studies in rats have morphologically determined the distribution of 5-HT release sites (boutons) in certain brain regions and have shown that 5-HT containing boutons form synaptic contacts that are either symmetric or asymmetric. In addition, 5-HT boutons can form synaptic triads with the pre- and postsynaptic specializations of either symmetrical or asymmetrical synapses. However, due to the labor intensive processing of serial sections required by electron microscopy, little is known about the neurochemical properties or the quantitative distribution of 5-HT triads within whole brain or discrete subregions. Therefore, we used a semi-automated approach that combines immunohistochemistry and high-resolution confocal microscopy to label serotonin transporter (SERT) immunoreactive axons and reconstruct in 3D their distribution within limbic brain regions. We also used antibodies against key pre- (synaptophysin) and postsynaptic components of excitatory (PSD95) or inhibitory (gephyrin) synapses to (1) identify putative 5-HTergic boutons within SERT immunoreactive axons and, (2) quantify their close apposition to neurochemical excitatory or inhibitory synapses. We provide a 5-HTergic axon density map and have determined the ratio of synaptic triads consisting of a 5-HT bouton in close proximity to either neurochemical excitatory or inhibitory synapses within different limbic brain areas. The ability to model and map changes in 5-HTergic axonal density and the formation of triadic connectivity within whole brain regions using this rapid and quantitative approach offers new possibilities for studying neuroplastic changes in the 5-HTergic pathway.


Antibiotic sensitivity of isolates of Pseudomonas aeruginosa in Buraidah, Saudi Arabia.
A study was carried out to determine the pattern of in vitro antibiotic sensitivity of a cross section of the isolates of Pseudomonas aeruginosa recovered from diverse clinical sources during a one year period. One hundred and eighty-six isolates were investigated by disc diffusion method employing multidiscs. Majority of the isolates were sensitive to amikacin (89.7%), tobramycin (75.81%), norfloxacin (68.48%), piperacillin (68.25%), and ceftazidime (58.81%). Other antibiotics were effective for a lesser number of isolates. A few isolates were simultaneously resistant to several antibiotics, viz. gentamicin, carbenicillin, tobramycin, ceftazidime and augmentin. The significance of the findings is discussed.


Crystallographically aligned carbon nanotubes grown on few-layer graphene films.
Carbon nanotubes are grown on few-layer graphene films using chemical vapor deposition without a carbon feedstock gas. We find that the nanotubes show a striking alignment to specific crystal orientations of the few-layer graphene films. The nanotubes are oriented predominantly at 60 degree intervals and are offset 30 degrees from crystallographically oriented etch tracks, indicating alignment to the armchair axes of the few-layer graphene films. Nanotubes grown on various thicknesses of few-layer graphene under identical process conditions show that the thinnest films, in the sub-6 atomic layer regime, demonstrate significantly improved crystallographic alignment. Intricate crystallographic patterns are also observed having sharp kinks with bending radii less than the ∼10 nm lateral resolution of the electron and atomic force microscopy used to image them. Some of these kinks occur independently without interactions between nanotubes while others result when two nanotubes intersect. These intersections can trap nanotubes between two parallel nanotubes resulting in crystallographic back and forth zigzag geometries. These interactions suggest a tip-growth mechanism such that the catalyst particles remain within several nanometers of the few-layer graphene surface as they move leaving a nanotube in their wake.


Relativistic potential energy surfaces of initial oxidations of Si(100) by atomic oxygen: the importance of surface dimer triplet state.
The non-relativistic and relativistic potential energy surfaces (PESs) of the symmetric and asymmetric reaction paths of Si(100)-2×1 oxidations by atomic oxygen were theoretically explored. Although only the singlet PES turned out to exist as a major channel leading to "on-dimer" product, both the singlet and triplet PESs leading to "on-top" products are attractive. The singlet PESs leading to the two surface products were found to be the singlet combinations (open-shell singlet) of the low-lying triplet state of surface silicon dimer and the ground (3)P state of atomic oxygen. The triplet state of the "on-top" product can also be formed by the ground singlet state of the surface silicon dimer and the same (3)P oxygen. The attractive singlet PESs leading to the "on-dimer" and "on-top" products made neither the intersystem crossings from triplet to singlet PES nor high energy (1)D of atomic oxygen necessary. Rather, the low-lying triplet state of surface silicon dimer plays an important role in the initial oxidations of silicon surface.


The efficacy of conbercept or ranibizumab intravitreal injection combined with laser therapy for Coats' disease.
The current treatment approaches for Coats' disease by intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents (ranibizumab or conbercept) combined with laser therapy were evaluated for the efficacy during the treatment. The medical records of 28 patients diagnosed with Coats' disease followed by the treatment with intravitreal injection of anti-VEGF agents and laser therapies at Tianjin Medical University Eye Hospital and Hebei Eye Hospital during July 2012 and October 2017 were reviewed retrospectively. Clinical outcomes were recorded with a minimum follow-up of 6 months. The patients were divided into ranibizumab- and conbercept-treated groups, as well as based on age: pediatric and adult groups. Twenty-eight patients were involved in this study. The average number of the injections was 2.82 ± 0.98. Laser photocoagulation was conducted in all patients, and the average number of lasers was 2.63 ± 0.74. The average follow-up period was 24.29 ± 9.85 months. Fourteen patients (50%) were stable, 12 (43%) patients were improved, and 2 patients (7%) showed recurred subretinal fluid and exudation. The final best corrected visual acuity (BCVA) increased markedly after intravitreal injection of ranibizumab or conbercept combined with laser therapy (p = 0.029, p = 0.009, respectively). The number of injections and lasers between conbercept and ranibizumab groups did not vary significantly (p = 0.160, p = 0.573, respectively). Nine patients (60%) in the ranibizumab-treated group and five (38%) in the conbercept-treated group reached a stable phase, and five (33%) and seven (54%) patients got the vision improved after treated with ranibizumab or conbercept, respectively. In pediatric and adult groups, the initial and final BCVA differed significantly (p = 0.03, p = 0.008, respectively). However, the injection number was remarkably different (p = 0.02), while the laser numbers did not have any markedly difference (p = 0.38). Intravitreal injection of ranibizumab or conbercept combined with laser therapy is an effective therapeutic option in Coats' disease. Moreover, the intravitreal injection of ranibizumab or conbercept had no significant adverse effects and appeared to offer visual improvement in Coats' disease.


[The histochemical diagnosis of Hirschsprung's disease according to Meier-Ruge (author's transl)].
The diagnosis of Hirschsprung's disease by histochemical techniques as proposed by Meier-Ruge, especially the detection of increased acetylcholine-esterase activity in rectal mucosal biopsy, provides an essential diagnostic improvement. This was confirmed by own experiences in 92 cases. The complicationless mucosal biopsy helps to avoid the more dangerous deep transmural biopsies. Furthermore, the intraoperative diagnosis of the aganglionary or hypoganglionary segment can be improved by histochemical demonstration of dehydrogenases in the intramural parasympathetic plexus. By these means it becomes easy to localize the correct position of the enterostoma as well as to determine the length of the segment to be resected.


Ultrasound Appearance of the Migration of Tendon Calcifications.
Calcific tendinopathy (CTe) is a frequent disorder related to the deposition of calcium hydroxyapatite crystals within tendons. Ultrasound has been shown to be an excellent imaging modality for the evaluation of CTe. During the resorptive phase of CTe, calcium deposits may migrate inside the tendons or in neighboring tissues and lead to local inflammation and severe pain. In this pictorial essay, we describe the ultrasound appearance of a spectrum of CTe migrations. Knowledge of the different migration patterns can help sonologists in their detection and in establishing the correct diagnosis.


Gender differences in the brain: implications for the study of human alcoholism.
Gender differences in alcohol intake and response to alcohol may be influenced by basic variations in the organization and modulation of male and female brains. Although a number of genetic, social, environmental, and metabolic factors have been proposed to explain the gender differences observed in risk for alcoholism, alcohol intake, and medical consequences of excessive alcohol intake, very little attention has been given to the role of gender differences in the brain regarding alcohol use. Recent evidence documents the influence of neurosteroids on neurotransmitter activity in the brain and the impact of alcohol on neurosteroid levels. Neurosteroids are found in different levels in males and females during development and throughout life, depending on factors such as age, stage of development, estrous and menstrual cycles, and stress. This study discusses the hypothesis that many of the gender differences observed concerning alcohol use and misuse are determined by gender differences in the brain, which in turn differentially influence the behavioral and neurochemical responses of males and females to alcohol.


Minimizing Stress Shielding and Cement Damage in Cemented Femoral Component of a Hip Prosthesis through Computational Design Optimization.
The average life expectancy of many people undergoing total hip replacement (THR) exceeds twenty-five years and the demand for implants that increase the load-bearing capability of the bone without affecting the short- or long-term stability of the prosthesis is high. Mechanical failure owing to cement damage and stress shielding of the bone are the main factors affecting the long-term survival of cemented hip prostheses and implant design must realistically adjust to balance between these two conflicting effects. In the following analysis we introduce a novel methodology to achieve this objective, the numerical technique combines automatic and realistic modeling of the implant and embedding medium, and finite element analysis to assess the levels of stress shielding and cement damage and, finally, global optimization, using orthogonal arrays and probabilistic restarts, were used. Applications to implants, fabricated using a homogeneous material and a functionally graded material, were presented.


Polymorphism of Clara cell 10-kD protein gene of sarcoidosis.
Clara cell 10-kD protein (CC10) exhibits potent antiinflammatory properties. G38A polymorphism was found in the CC10 gene. We investigated the genetic influence of the allele on the development of sarcoidosis using case control analysis in a Japanese population (265 sarcoidosis cases and 258 control subjects). The A allele frequency in sarcoidosis cases (45.1%) was significantly higher than healthy control subjects (34.9%, p = 0.0002). According to outcomes, we divided 223 patients with follow-up periods of 3 years or more into two subgroups (55 progressive and 168 regressive disease). The A allele frequency in patients with progressive disease was significantly higher than control subjects (odds ratio = 4.55; 95% confidence interval, 2.97-6.97; p < 0.0001), whereas that of regressive disease was not. The A/A genotypes had significantly lower bronchoalveolar lavage fluid CC10 levels than the G/G (nonsmokers, p = 0.0054, and smokers, p = 0.0045) and G/A genotypes (nonsmokers, p = 0.0022, and smokers, p = 0.0402). The reporter gene assay showed significantly lower reporter activities in the presence of interferon-gamma for the 38A construct than the 38G construct (p = 0.0177). The G38A polymorphism in the CC10 gene may influence protein expression and be associated with the development of progressive sarcoidosis.


Objective burden and emotional distress in parents of children with type 1 diabetes.
The management of childhood type 1 diabetes requires the active participation of parents. The aim of the present study was to describe the main characteristics of parents of children with type 1 diabetes, including objective burden regarding time spent on diabetes care, emotional distress (exhaustion, need for respite, quality of life), and symptoms of depression as well as anxiety. In this observational study, parents of children with type 1 diabetes completed a questionnaire, anonymously. Different questions were asked to the parent about the objective burden of diabetes and its repercussion, their exhaustion and need for respite. Two validated instruments (HADS, WHOQOL-BREF) have been integrated into the questionnaire. Eighty eight parents were included in the study. Among them, 76 (86%) were mothers. All the parents with a child aged 6 years or younger (10/10) reported having to take care of their child's diabetes twice or more a day, this was the case for 37/39 (94.9%) parents of children aged 7 to 13, and for 16/36 (44.4%) of parents of children aged 14 years or above. In the total population, 33/86 (38.4%) parents declared getting up every night because of their child's diabetes. The median daily time spent on diabetes management was 40 minutes. There were 54 parents (62.8%) who reported moderate-strong exhaustion, and 27 (30.7%) who expressed a moderate-strong need for respite. Regarding the result of the HADS, 46 parents (55.4%) reported symptoms of anxiety and/or depression. Parents of children with type 1 diabetes must carry out multiple daily care, at all times of day and night. Their emotional state can be impacted with, in particular, a risk of exhaustion. Screening for these difficulties should be a part of the overall management of a child with type 1 diabetes and his family to limit various complications.


Does Drying Affect Gel Networks?
The properties of low molecular weight gels are determined by the underlying, self-assembled network. To access information on the network, it is common for techniques to be used that require the gel to be dried, such as transmission electron microscopy or scanning electron microscopy. The implicit assumption is that this drying has no bearing on the data collected. Here, we discuss the validity of this assumption.


Effects of peritoneal macrophage autophagy on the immune function of sepsis mice.
To investigate the effect of peritoneal macrophage autophagy on immune function in sepsis mice. Seventy-two male BALB/C mice were intraperitoneally injected with LPS to induce sepsis. The mice were randomly divided into six groups: LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h. LPS with a dose of 10 mg/kg was intraperitoneally injected into the abdominal cavity of the sepsis mice, and the control group was injected with the same dose of saline. ELISA was used to detect the concentrations of inflammatory factors IL-2, IL-10 and TNF-α in the peripheral blood, and the CD4+T/CD8+T ratio in the peripheral blood was detected by flow cytometry. The expression levels of LC3II and Beclin-1/beta-action in the mouse macrophages were measured using Western blot to determine the level of autophagy. The expression levels of LC3II and Beclin-1 were significantly higher in the peritoneal macrophages of the mice from the LPS+2 h group than in those of the mice from the normal group (P<0.05). Meanwhile, these levels continuously declined in the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups (P<0.05). The peripheral blood CD4+T/CD8+T cell ratio was significantly higher in the LPS+2 h and LPS+6 h groups than in the normal group (P<0.05). The ratio peaked at 6 h and then continuously declined (P<0.05). Furthermore, the concentrations of IL-2 and Tnf-α were significantly higher in the peripheral blood serum of the LPS+2 h, LPS+6 h and LPS+12 h groups than in those of the normal group (P<0.05). The peak was observed at 12 h followed by a continuous decline in the LPS+24 h and 3 LPS+6 h groups (P<0.05). The peripheral serum IL-10 concentration was significantly higher in the LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups than in the normal group (P<0.05). In the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups, the peritoneal macrophages LC3II, Beclin-1 and peripheral serum CD+4T/CD+8T ratio correlation index R2=0.716 (P=0.043), R2=0.954 (P=0.023). Autophagy in peritoneal macrophages plays an important role in the immune function of sepsis mice. In addition, the autophagy of peritoneal macrophages and the immune function of sepsis mice are strongly correlated. Furthermore, macrophage autophagy plays an important role in the immune function changes in sepsis mice, and the underlying mechanism may be involved in inflammation and macrophage antigen presentation by regulating the secretion of inflammatory cytokines and lymphocyte apoptosis antagonism.


Detection and characterization of cellular EGR-1 binding to its recognition site.
Most of what is known of the Egr-1 DNA binding site GCGGGGGCG was originally identified by experiments using DNA sequences and bacterially expressed or in vitro translated EGR-1 protein. Here we report the binding of cellular EGR-1 protein derived from HeLa, mouse and human fibroblasts to its consensus sequence. Binding is strongly but transiently stimulated in these cells by serum, phorbol ester, or by okadaic acid, an inhibitor of protein serine/threonine phosphatases 1 and 2A, suggesting the regulation of this gene expression and its DNA binding activity to be under the control of protein kinase(s) and phosphatase(s). When EGR-1 synthesis is stimulated under the above conditions, binding of the transcription factor Sp1 to its recognition site in the Egr-1 promoter is reduced with a concomitant appearance of EGR-1 DNA binding. This is likely a result of competition between Sp1 and the newly synthesized EGR-1, since there is a partial overlap in the binding sequences recognized by these proteins. In cotransfection experiments EGR-1 activated transcription through multiple copies of GCGGGGGCG 5' to a minimum promoter of c-fos. Interestingly, EGR-1 is shown to down-regulate the transcription of its own gene expression, whereas Sp1 activated Egr-1 gene expression. The detection of cellular EGR-1 binding to the Egr-1 consensus sequence in the different cell types provides a model for studying the mechanism by which an immediate-early gene is regulated by various ligands.


Colossal absorption of molecules inside single terahertz nanoantennas.
Molecules have extremely small absorption cross sections in the terahertz range even under resonant conditions, which severely limit their detectability, often requiring tens of milligrams. We demonstrate that nanoantennas tailored for the terahertz range resolves the small molecular cross section problem. The extremely asymmetric electromagnetic environment inside the slot antenna, which finds the electric field being enhanced by thousand times with the magnetic field changed little, forces the molecular cross section to be enhanced by >10(3) accompanied by a colossal absorption coefficient of ~170,000 cm(-1). Tens of nanograms of small molecules such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and lactose drop-cast over an area of 10 mm(2), with only tens of femtograms of molecules inside the single nanoslot, can readily be detected. Our work enables terahertz sensing of chemical and biological molecules in ultrasmall quantities.


In vitro autoradiographic visualization of occupied estrogen receptors in the rat brain with an iodinated estrogen ligand.
Methods have been developed for the selective measurement of occupied estrogen receptors (ER) in brain tissue sections. Cryostat sections of unfixed tissue were incubated with radiolabeled estrogen at physiological temperatures, displacing endogenous receptor-bound estrogen by radioligand and thereby allowing the receptor complexes to be visualized autoradiographically after washing to remove nonspecifically bound steroid. The resultant autoradiographs were analyzed by computer-assisted densitometry. Synthetic 11 beta-methoxy-substituted radiolabeled estrogens gave the best autoradiographic images, as a result of reduced nonspecific labeling, although [3H]-estradiol was also used successfully. With the synthetic ER ligand 11 beta-methoxy 16 alpha-[125I]-iodo-estradiol, exposure times of less than 24 hr generated acceptable autoradiographs; with 3H-labeled estrogens, exposures of 3 months or more may be required. The method is sufficiently sensitive to detect physiological changes in ER occupation and to allow determination of receptor affinities and saturation binding capacities in discrete cell groups identified in sections from individual animals.


Effects of hypolipidemic drugs nafenopin and clofibrate on phenotypic expression and cell death (apoptosis) in altered foci of rat liver.
Phenotypically altered liver foci were produced in female Wistar rats by a single dose of N-nitrosomorpholine followed by promotion with phenobarbital (PB) for 20 or 28 weeks. Then treatment was changed to either hexachlorocyclohexane (HCH), or cyproterone acetate (CPA), or nafenopin (Naf) or clofibrate (Clof), two hypolipidemic drugs. Foci were identified by a positive reaction for gamma-glutamyl-transpeptidase (GGT) and other cytological markers. HCH and CPA could substitute for PB as foci promoters; in contrast, Naf and Clof decreased expression of GGT in foci resulting in a decline of number and area of detectable foci, effects particularly pronounced with Naf. Immunohistochemical investigations of serial sections revealed that Naf also reduced expression of the altered phenotype when cytochrome P450-PB and pyruvate kinase (type L) were used as foci markers, but not when glutathione-S-transferase B (GST-B) was used. Thus, the number of foci with enhanced GST-B did not decline significantly after the change from PB to Naf treatment. Furthermore, the reduction of GGT and the decrease of foci number during Naf treatment were not associated with increased evidence of cell death by apoptosis in foci, in contrast to the situation after PB withdrawal. These findings strongly suggest that the disappearance of GGT-positive foci after Naf is due to a phenotypic change resulting in a suppression of GGT expression rather than to physical elimination of foci.


Aerosol-Assisted Fine-Tuning of Optoelectrical Properties of SWCNT Films.
We propose a novel, scalable, and simple method for aerosol doping of single-walled carbon nanotube (SWCNT) films. This method is based on aerosolization of a dopant solution (HAuCl4 in ethanol) and time-controlled deposition of uniform aerosol particles on the nanotube film surface. The approach developed allows fine-tuning of the SWCNT work function in the range of 4.45 (for pristine nanotubes) to 5.46 eV, controllably varying the sheet resistance of the films from 79 to 3.2 Ω/□ for the SWCNT films with 50% transmittance (at 550 nm). This opens a new avenue for traditional and flexible optoelectronics, both to replace existing indium-tin oxide electrodes and to develop novel applications of the highly conductive transparent films.


Pure and functionally homogeneous recombinant retinoid X receptor.
Mouse retinoid X receptor alpha (RXR alpha) lacking the amino-terminal region A/B (RXR alpha delta AB) has been purified to more than 98% purity and functional homogeneity from bacterial and baculovirus-based recombinant expression systems with yields of 2-8 mg/liter of culture. The purified protein is soluble, and fluorescence quenching analysis demonstrated that it binds its cognate ligand 9-cis-retinoic acid (9-cis-RA) stoichiometrically, and with high affinity. Compared with RXR delta AB expressed in COS-1 cells, bacterially and baculovirus-expressed proteins bind approximately 10 and 5 times less efficiently to direct repeat 1 (DR1) DNA elements, respectively, suggesting that animal cell-specific modification of RXR or interaction with other animal cell-specific factors may modulate DNA binding. 9-cis-RA did not stimulate DR1 binding of functional RXR delta AB expressed in Escherichia coli, Sf9 or COS-1 cells. The previously reported ligand effect that can be observed with in vitro made receptor may therefore be a consequence of a conformational stabilization of improperly folded in vitro synthesized protein.


Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG-PLA Conjugate for Tuning Immunity.
Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion. A peptide/polymer conjugate, named LD-indolicidin-PEG-PLA, was synthesized by conjugation of the amine end-group of LD-indolicidin to the N-hydroxysuccinimide-activated carboxyl end-group of PEG. As an adjuvant for cancer immunotherapeutic use, TAA vaccine candidate formulated with the LD-indolicidin-PEG-PLA-stabilized squalene-in-water emulsion could effectively help to elicit a T helper (Th)1-dominant antigen-specific immune response as well as antitumor ability, using ovalbumin (OVA) protein/EG7 cells as a TAA/tumor cell model. Taken together, these results open up a new approach to the development of immunomodulatory antigen delivery systems for vaccine adjuvants and cancer immunotherapy technologies.


A shorter and multidimensional version of the Gambling Attitudes and Beliefs Survey (GABS-23).
The Gambling Attitudes and Beliefs Survey (GABS) is a questionnaire which explores gambling-related dysfunctional beliefs in an unidimensional way. The present research aims to investigate the dimensionality of the scale. 343 undergraduate student gamblers and 75 pathological gamblers seeking treatment completed the GABS and the south oaks gambling screen. Exploratory and confirmatory factor analyses revealed that the original one-factor structure of the GABS did not fit the data effectively. We then proposed a shorter version of the GABS (GABS-23) with a new five-factor structure, which fitted with the data more efficiently. The comparisons between students (problem vs. non-problem gamblers) and pathological gamblers seeking treatment indicated that the GABS-23 can discriminate between problem and non-problem gamblers as efficiently as the original GABS. To ensure the validity and the stability of the new structure of the GABS-23, analyses were replicated in an independent sample that consisted of 628 gamblers (256 non problem gamblers, 169 problem gamblers who are not treatment-seeking and 203 problem gamblers seeking treatment). Analyses showed satisfactory results, and the multidimensional structure of the GABS-23 was then confirmed. The GABS-23 seems to be a valid and useful assessment tool for screening gambling-related beliefs, emotions and attitudes among problem and non-problem gamblers. Moreover, it presents the advantage of being shorter than the original GABS, and of screening irrational beliefs and attitudes about gambling in a multidimensional way. The five-factor model of the GABS-23 is discussed based on the theory of locus of control.


Nursing intellectual capital theory: testing selected propositions.
To test the selected propositions of the middle-range theory of nursing intellectual capital. The nursing intellectual capital theory conceptualizes nursing knowledge's influence on patient and organizational outcomes. The theory proposes nursing human capital, nurses' knowledge, skills and experience, is related to the quality of patient care and nurse recruitment and retention of an inpatient care unit. Two factors in the work environment, nurse staffing and employer support for nurse continuing professional development, are proposed to influence nursing human capital's association with patient and organizational outcomes. A cross-sectional survey design. The study took place in 2008 in six Canadian acute care hospitals. Financial, human resource and risk data were collected from hospital departments and unit managers. Clearly specified empirical indicators quantified the study variables. The propositions of the theory were tested with data from 91 inpatient care units using structural equation modelling. The propositions associated with the nursing human capital concept were supported. The propositions associated with the employer support for nurse continuing professional development concept were not. The proposition that nurse staffing's influences on patient outcomes was mediated by the nursing human capital of an inpatient unit, was partially supported. Some of the theory's propositions were empirically validated. Additional theoretical work is needed to refine the operationalization and measurement of some of the theory's concepts. Further research with larger samples of data from different geographical settings and types of hospitals is required to determine if the theory can withstand empirical scrutiny.


Smoking behaviors and intentions among current e-cigarette users, cigarette smokers, and dual users: A national survey of U.S. high school seniors.
E-cigarette use among adolescents has increased significantly in recent years, but it remains unclear whether cigarette smoking behaviors and intentions for future cigarette smoking differ among current (i.e., 30-day) non-users, only e-cigarette users, only cigarette smokers, and dual users. A nationally representative sample of 4385 U.S. high school seniors were surveyed during the spring of their senior year via self-administered questionnaires in 2014. An estimated 9.6% of U.S. high school seniors reported current e-cigarette use only, 6.3% reported current cigarette smoking only, and 7.2% reported current dual use of e-cigarettes and cigarette smoking. There were no significant differences between current only cigarette smokers and dual users in the odds of early onset of cigarette smoking, daily cigarette smoking, intentions for future cigarette smoking, friends' cigarette smoking behaviors, attempts to quit cigarette smoking, or the inability to quit cigarette smoking. Adolescents who only used e-cigarettes had higher odds of intentions for future cigarette smoking in the next 5years (AOR=2.57, 95% CI: 1.21-5.24) than current non-users. Dual users and only cigarette smokers had higher odds of cigarette smoking behaviors and intentions for future cigarette smoking than non-users or only e-cigarette users. Adolescents who engage in current dual use have cigarette smoking behaviors and intentions for future cigarette smoking that more closely resemble cigarette smokers than e-cigarette users. Adolescents who only use e-cigarettes have higher intentions to engage in future cigarette smoking relative to their peers who do not engage in e-cigarette use or cigarette smoking.


A transcutaneous bone digitizer for minimally invasive registration in orthopedics: a real-time focused ultrasound beam approach.
Computer-guided navigation of surgical tool position in computer-assisted orthopedic systems requires the registration of computer tomographic (CT) images with underlying bone. This process is presently performed by manually digitizing points on bone with a pointer and aligning them to a preoperative CT scan. We propose the use of ultrasound to obtain points on bone transcutaneously. A custom-made A-mode probe features a modular lens focusing system and a one-step calibration method. A stable and precise echo detection algorithm is also implemented. The accuracies of three signal detection algorithms--standard deviation, cross-correlation (XCORR) and short-time Fourier transform--were compared using a known reflected signal. XCORR showed the most accurate and stable operation. To test our method of obtaining bone surface points, a plastic model of the fourth human lumbar vertebra was CT scanned and then immersed in a water bath. Six surface registrations of the vertebra using an accurate pointing device were compared to ten registrations obtained using the US probe (using the XCORR algorithm). Student's T-test showed no significant difference in error between the two methods, proving that ultrasound registration, using our method, is equivalent to the more conventional pointer method.


Results of the VALOR II trial of the Medtronic Valiant Thoracic Stent Graft.
The 1-year results of endovascular exclusion of degenerative descending thoracic aortic aneurysms (DTA) with the Valiant Thoracic Stent Graft (Medtronic Vascular, Santa Rosa, Calif) have been previously reported. With long-term follow-up now complete, the 5-year results are reported. The VALOR II trial (Evaluation of the Clinical Performance of the Valiant Thoracic Stent Graft System in the Treatment of Descending Thoracic Aneurysms of Degenerative Etiology in Subjects Who Are Candidates for Endovascular Repair) was a prospective, nonrandomized trial of the Valiant Thoracic Stent Graft system in patients with degenerative DTA. The trial involved 24 sites in the United States and enrolled patients between December 2006 and September 2009. Standard follow-up included physical examination, computed tomography, and chest radiography through 5 years. The study enrolled 160 patients. The average age was 72.2 years (range, 36-85 years), 95 (59%) were men, 150 (94%) had hypertension, and 26 (16%) had renal insufficiency. There were 50 patients (31%) who presented with symptoms; back pain was the most common (34 [68%]). The average aneurysm diameter was 57 mm (range, 32-96 mm). There were 103 patients (64%) with a fusiform aneurysm and 57 (36%) with a saccular aneurysm or penetrating ulcer. Two or more devices were implanted in 126 patients (79%), and the maximum number of grafts implanted was four. There were 54 deaths during the study. The 5-year actuarial survival was 64%. There were eight aneurysm-related deaths (5 deaths ≤30 days of implant), and the 5-year freedom from aneurysm-related death was 95%. There was one conversion to open repair at 36 months. Eleven patients underwent 13 secondary procedures (9 for endoleak, 3 for aneurysm expansion, and 1 rupture). Follow-up imaging was available at 5 years for 56 patients. The average aortic diameter decreased >5 mm in 27 patients (48%), increased >5 mm in 6 patients (11%), and remained unchanged in 23 (41%). The VALOR II 5-year results demonstrate that the reintervention and aneurysm-related death rates are low. The Valiant Thoracic Stent Graft is an effective treatment of degenerative DTA.


Hydrothermal growth of lanthanide borosilicates: a useful approach to new acentric crystals including a derivative of cappelenite.
The reaction of barium borosilicate glasses in hydrothermal fluids with NaOH mineralizer at ca. 600-650 °C in the presence of various sources of Eu(3+) ions leads to a new series of noncentrosymmetric single crystals characterized by single-crystal X-ray diffraction. Under three slightly different reaction modifications, three new Eu(3+)-containing noncentrosymmetric single crystals were isolated and characterized. Using a barium borosolicate glass with Eu(2)O(3) added to the reaction mixture led to NaBaEuSi(3)O(9) (1), which crystallizes in the noncentrosymmetric orthorhombic space group P2(1)2(1)2(1) with unit cell parameters a = 5.6373(11) Å, b = 11.483(2) Å, and c = 12.535(2) Å and consists of Eu(3+) ions linked by Si(3)O(9)(6-) rings. Using a similar glass feedstock with Eu(3+) included in the starting glass composition led to the compound NaBa(3)Eu(3)Si(6)O(20) (2), which was determined in the noncentrosymmetric polar space group Ama2 with unit cell parameters a = 14.777(3) Å, b = 23.926(5) Å, and c = 5.5533(11) Å. It is constructed of individual islands of Si(4)O(13)(10-) and lone Si(2)O(7)(6-) building fragments. Finally, use of the Eu-containing glass along with additional Eu(2)O(3) led to the compound BaEu(6)(Si(3)B(6)O(24))(OH)2 (3), which crystallizes in the polar space group P6mm with a = 10.8074(15) Å and c = 4.7296(9) Å. It is related to the rare and poorly understood mineral cappelenite Ba(Y,RE)(6)(Si(3)B(6)O(24))F(2) and contains six-membered tetrahedral borate rings linked by silicate tetrahedra. The high percentage of noncentrosymmetric crystals obtained from of a simple borosilicate glass starting material, along with various straightforward chemical additives, suggests strongly that many more noncentrosymmetric crystals can be isolated from this general system.


Maternal serum cytokines in preterm premature rupture of membranes.
To estimate whether maternal serum interleukin (IL)-6 or granulocyte colony-stimulating factor (G-CSF) obtained daily are elevated in women with preterm premature rupture of membranes who develop funisitis. Daily blood samples were obtained from women with preterm premature rupture of membranes and analyzed for IL-6 and G-CSF by enzyme-linked immunosorbent assay. Funisitis was determined by placental examination. Observations were stratified based on the presence or absence of funisitis and analyzed. Proportional hazards models were used to evaluate time-to-delivery on the basis of diagnostic IL-6 and G-CSF levels, determined by receiver operating characteristic curve analysis. Of the 107 patients available for analysis, 54 (50%) had evidence of funisitis after delivery. Patients with funisitis were more likely to deliver at an earlier gestational age (28.5 weeks compared with 31.5 weeks, P<.001) and have Medicaid insurance (57% compared with 39%, P=.04). Serum IL-6 and G-CSF were elevated 24 to 48 hours before delivery in women with preterm premature rupture of membranes with funisitis compared with those without funisitis (IL-6, 7.5 compared with 2.8 pg/mL, P<.001; G-CSF, 121.7 compared with 56.9 pg/mL, P=.002). Using values identified by the receiver operating characteristic curve, elevated serum IL-6 in the interval 24-72 hours before delivery was significantly associated with funisitis (P<.03), even after controlling for gestational age and insurance status. Maternal serum IL-6 and G-CSF appear to be biomarkers in the identification of women with preterm premature rupture of membranes likely to develop funisitis. II.


A Novel Link Between Adipokines And Lipoprotein (A) To Contemplate Their Diagnostic Role In Patients With Stemi And Nstemi.
Early detection of cardiac events allow better and cost-effective triage and welltimed management of these patients. Study was conducted to evaluate the prognostic significance of plasma adiponectin, resistin and lipoprotein (a) in a group of patients with ST segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. These parameters were also compared with other predictors like troponin T, troponin I and CK-MB. Present study was based on the 100 patients with AMI of whom 52 had a diagnosis of STEMI, and 48 had NSTEMI. Duration of study was January to June 2015. Patients having chest pain that was indicative of myocardial ischemia within first 12 hours after the onset of symptoms were included in the study. Adiponectin, Lp (a), resistin, troponin T and troponin I were estimated using ELISA method. Level of CK-MB was measured by Auto-analyser using standard kit of Merck. Mean age of patients with STEMI was 52.32 years and with NSTEMI it was 48.17 years. Mean value of BMI of patients with STEMI was 28.33 and with NSTEMI was 25.22 Kg/m2. Duration of chest pain in patients with STEMI was 8.64 and patients with NSTEMI it was 16.52hours with highly significant difference (p<0.001). History of smoking in patients with STEMI was more as compared to the patients with NSTEMI. Level of CPK, adiponectin and lipoprotein (a) was raised in patients with STEMI as compared to patients with NSTEMI but significant difference was only found in levels of CPK (p<0.001) and in adiponectin (p<0.05). Level of serum CK-MB, TnT, TnI and resistin was raised in patients with NSTEMI as compared to patients with STEMI but significant difference (p<0.001) was only observed in serum troponin I concentration. It is concluded that the incidence of STEMI and NSTEMI is similar in our patients. However, the markers of STEMI are increased level of adiponectin and Lp(a) and the markers of NSTEMI are troponins especially troponin I, resistin and CKMB.


3-Methylglutaconyl-Coenzyme-A Hydratase Deficiency and the Development of Dilated Cardiomyopathy.
A 25-year-old Canadian male with a history of 3-methylglutaconyl-coenzyme-A hydratase deficiency, also known as 3-methylglutaconic aciduria type I, a very rare inborn error of metabolism, presented with respiratory distress, nausea, vomiting and signs of multisystem organ failure due to a suspected underlying infectious process. An electrocardiogram revealed bilateral atrial enlargement and an elevated brain natriuretic peptide on the initial laboratory studies, which prompted a more thorough cardiac workup. The transthoracic echocardiogram revealed a dilated cardiomyopathy with severe systolic dysfunction. The deficient enzyme present in this patient is involved in the pathway of leucine catabolism and is particularly important in various tissues for energy production and sterol synthesis. The dilated cardiomyopathy in this patient possibly had a variety of potential mechanisms including: a mitochondrial myopathy due to the deficiency of this enzyme leading to a defect in energy production inside cardiac myocytes; or a direct toxicity from 3-methylglutaconic acid (3-MGA) and its toxic metabolites; or a cardiac dysfunction due to a variety of other potential mechanisms. In conclusion, this patient's clinical presentation suggested that 3-methylglutaconyl-CoA hydratase deficiency could cause a severe dilated cardiomyopathy and heart failure.


Transcriptional regulation of memory B cell development.
Abstract Antigen-reactive B cells in the spleen of mice immunized with T cell-dependent antigens generate antibody-producing foci in periarteriolar lymphoid sheaths (PALS) or migrate into follicles to form germinal centers. Germinal center B cells clonally expand, have somatic hypermutation in IgV-region genes, are selected by apoptosis on the basis of antigen-specific signals, and differentiate to memory B cells. Two transcription factors (Bcl6 and c-Fos) in B cells play a critical role in the development of germinal centers. (1) Bcl6 is highly expressed in germinal center B cells, and defects in B cells perturb the formation of germinal centers but not that of PALS-associated foci, indicating the essential role of Bcl6 in the differentiation. (2) Overexpression of c-Fos in germinal center B cells induces apoptosis and perturbs the formation of memory B cells. Overexpression of Bcl-2 cannot rescue c-Fos-induced apoptosis in germinal center B cells. Since c-Fos is induced in mature B cells which have reacted with antigens, and clonal deletion of self-reactive B cells is insensitive to overexpression of Bcl-2, c-Fos may play a causal role in the clonal deletion of germinal center B cells. Thus, these factors provide a unique opportunity to investigate the molecular mechanisms of memory B cell development.


5-azacytidine and decitabine monotherapies of myelodysplastic disorders.
To review and differentiate the pharmacology, toxicology, pharmacokinetics, and results of major clinical trials of 5-azacytidine (5-AzaC) and 5-aza-2'-deoxycytidine (decitabine) therapy of myelodysplastic disorders. A PubMed/MEDLINE search was conducted (1966-October 2004) using the following terms: DNA methylation, myelodysplastic disorders, 5-azacytidine, and 5-aza-2'-deoxycytidine (decitabine). Additional data sources included bibliographies from identified articles and manufacturer information. Clinical trials for the treatment of various malignancies by hypomethylating agents were selected from data sources. All published, major clinical trials evaluating 5-AzaC or decitabine in myelodysplastic disorders and transformed myeloid leukemia treatment were included. Myelodysplastic disorders are a group of bone marrow stem cell hyperplasias and dysplasias that result in ineffective hematopoiesis. Myelodysplastic disorders and transformed leukemia have poor prognosis and minimal response to chemotherapy. DNA hypomethylating agents have been shown to improve overall response rates (increased neutrophil, leukocyte, and platelet counts), time to leukemic progression, and quality of life compared with supportive therapy. The incidence of the most common adverse effects (nausea, vomiting, myelosuppression) can be reduced by low-dose, continuous, or extended-interval infusion. Since appropriate dosing schedules of decitabine are being investigated, comparison of the clinical effectiveness of 5-AzaC and decitabine would be premature at this time. DNA hypomethylating agents show promise as monotherapies of myelodysplastic disorders and transformed leukemia and may be useful as a component of combination chemotherapy of various malignancies.


Novel cyclic templates of alpha-MSH give highly selective and potent antagonists/agonists for human melanocortin-3/4 receptors.
In an effort to develop highly selective and potent agonists and/or antagonists for the hMC3 and hMC4 receptors, a new approach involving the use of linker arms and a backbone to side chain cyclization strategy was employed. Three key analogues were identified to have the required selectivity and potency at the hMC3 or hMC4 receptors, implicated to play pivotal roles in energy homeostasis and other biological effects. The novel cyclic peptide (O)C-CH(2)-CH(2)-C(O)-c-[His(6)-D-Phe(7)-Arg(8)-Trp(9)-Lys(10)]-NH(2) (1) was found to be a highly selective and potent agonist of the hMC4 receptor. Structure-activity studies have shown that replacing the succinyl linker arm of 1 by an o-phthalic acid group and substituting a D-Nal(2')(7) residue in place of D-Phe(7) results in a potent antagonist 7 at the hMC4 receptor. Furthermore, increasing the 23-membered lactam ring of 1 by one carbon atom (succinyl --> glutaric acid linker) gives a highly selective and potent antagonist 9 for the hMC3 receptor. Analogues 1, 7, and 9 therefore represent the first examples of a class of cyclic melanotropin ligands with high selectivity and defined biological activities at the physiologically important hMC3 and hMC4 receptors.


Daily Preharvest UV-C Light Maintains the High Stilbenoid Concentration in Grapes.
The fact that it is possible to induce stilbenoid synthesis in grapevine (Vitis vinifera) by UV-C light allows the possibility of stimulating grapevine phytoalexin production to increase disease resistance and immunity, and subsequently to limit the use of pesticides in vineyards. UV-C light was applied daily during three days before the harvesting of table grape variety Crimson seedless to study the accumulation of stilbenoid compounds during ripeness. The E-resveratrol concentration was monitored during daily preharvest UV-C light application and compared with that after a single application. Daily periodic preharvest UV-C light treatment showed a cumulative effect on grape stilbenoids. An 86-fold stilbenoid level increase (sum of E-resveratrol, E-piceatannol, ε-viniferin, E-piceid, isorhapontigenin, ω-viniferin, and Z-piceid) in grapes was achieved. The effects of UV-C light on stilbenoid in grape cane was also addressed for the first time. Stilbenoid oligomers such as hopeaphenol, ampelopsin A, and r-viniferin were quantified in cane samples. Quality grape parameters indicated an acceleration of ripening in UV-C samples.


Simple index for validity of the evaluation point for dosimetric verification results of intensity-modulated radiation therapy using a Farmer-type ionization chamber.
Based on a retrospective analysis, this study aims to develop a simple index for validity of the evaluation point for the dosimetric verification of intensity-modulated radiation therapy (IMRT). The results for the dosimetric verifications of a total of 69 IMRT plans were analyzed in this study. A Farmer-type ion chamber was used as a dose detector, and a solid water-equivalent phantom was used. Index values were obtained by dividing the difference between the maximum and minimum dosages by the mean dosage of the 69 plans, and the values were classified into five groups with index value <4, 4-8, 8-12, 12-16, and >16. A t-test was used to assess the statistical significance of the mean differences of the absolute values of the relative errors among these groups. We found that there was no significant difference between the groups with index value <4 and 4-8 (p = 0.152); however, there were significant differences between the other groups (p < 0.01). In addition, when the index values were smaller than 8, the pass ratio of 3% tolerance was 96.2% and the pass ratio of 5% tolerance was 99.9%. We observed that the smaller the index value, the smaller the uncertainty of the dose measurement. The results obtained in this study may prove to be useful for accurate dosimetric verifications of IMRTs when ion chambers are used.